Certal, Victor published the artcileDiscovery and Optimization of Pyrimidone Indoline Amide PI3Kβ Inhibitors for the Treatment of Phosphatase and Tensin Homologue (PTEN)-Deficient Cancers, Recommanded Product: 4-Chloroindoline, the main research area is PI3Kbeta phosphatase tensin homolog PTEN neoplasm structure activity preparation.
Compelling mol. biol. publications have reported the implication of phosphoinositide kinase PI3Kβ in PTEN-deficient cell line growth and proliferation. These findings supported a scientific rationale for the development of PI3Kβ-specific inhibitors for the treatment of PTEN-deficient cancers. This paper describes the discovery of 2-[2-(2,3-dihydro-indol-1-yl)-2-oxo-ethyl]-6-morpholin-4-yl-3H-pyrimidin-4-one and the optimization of this new series of active and selective pyrimidone indoline amide PI3Kβ inhibitors. 2-[2-(2-Methyl-2,3-dihydro-indol-1-yl)-2-oxo-ethyl]-6-morpholin-4-yl-3H-pyrimidin-4-one (I), identified following a carefully designed Me scan, displayed improved physicochem. and in vitro pharmacokinetic properties. Structural biol. efforts enabled the acquisition of the first x-ray cocrystal structure of p110β with the selective inhibitor compound I bound to the ATP site. The nonplanar binding mode described herein is consistent with observed structure-activity relationship for the series. Compound I demonstrated significant in vivo activity in a UACC-62 xenograft model in mice, warranting further preclin. investigation. Following successful development, compound 28 entered phase I/Ib clin. trial in patients with advanced cancer.
Journal of Medicinal Chemistry published new progress about Antitumor agents. 41910-64-9 belongs to class indole-building-block, name is 4-Chloroindoline, and the molecular formula is C8H8ClN, Recommanded Product: 4-Chloroindoline.
Referemce:
Indole alkaloid derivatives as building blocks of natural products from Bacillus thuringiensis and Bacillus velezensis and their antibacterial and antifungal activity study,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles